In recent years, new psychoactive plants have been emerging on the streets. An example is the strong hallucinogenic mint Salvia divinorum and its active metabolite salvinorin A. The use of this hallucinogen, unregulated by Federal and most State laws, is spreading across the country and globe. Since 1970 when the Controlled Substances Act was enacted into law by Federal Government and cannabis (marijuana) was placed in the Schedule I, a number of marijuana substitutes or alternatives started to appear on the market. These plants are easily obtained on numerous internet sites and have a high potential of becoming street drugs in the near future. Despite their ready availability, the psychopharmacology of these plants and their metabolites is largely unknown. In most cases, neither the active constituents of these plants nor the mechanisms of their interactions with the central nervous system have been determined. The purpose of this project is the study of the chemistry and pharmacology of psychoactive plants used as marijuana substitutes. For this project, we have selected five marijuana-substitute plant species with prominent internet sales offers. We propose to biologically evaluate these plants against the battery of CNS receptors under the NIMH Psychoactive Drug Screening Program at the University of North Carolina at Chapel Hill, and isolate the active secondary metabolites responsible for their psychotropic effects. In the long-term, new ligands to CNS receptors discovered and developed in this project will contribute to better knowledge of the central nervous system functions and its disorders. To achieve these goals, the following specific aims will be pursued: 1. Acquisition of selected plant species from popular internet sources and professional entities. 2. Identification of active metabolites by vaporization/sublimation process 3. Selective extraction of biological material. 4. Biological evaluation of extracts for affinity to CNS neurotransmitters receptors. 5. Bioassay-guided fractionation and isolation of active secondary metabolites. 6. Structure elucidation of isolated metabolites and their biological re-evaluation in the specific receptor systems. The data generated by this project will form a basis for further research and provide preliminary results for seeking more extensive funding. PUBLIC HEALTH RELEVANCE: With the growing number of psychoactive plants and substances on the streets, concern for people's health, especially that of youth, becomes an increasingly important issue. Many of the emerging hallucinogenic plants advertised via Internet and used as marijuana substitutes are poorly studied. We do not know their mechanism of action in the central nervous system, their potential to become addictive drugs of abuse, their toxicity to vital organs and systems of the human body or other side effects. Our project to study the psychopharmacology of plants used as marijuana substitutes will address these issues and provide information to further research in this area.